It is estimated that 10% of the population is affected by sensorineural or """"""""nerve"""""""" deafness that usually arises from sensory hair cell loss or damage. Sensory deficits resulting from hair cell loss have been considered irreversible because the production of human hair cells ceases before birth. In contrast, hair cells are produced postembryonically in the ears of cold-blooded and some warm-blooded vertebrates (birds); in some, thousands of new hair cells can be replaced through trauma-evoked regenerative proliferation. Evidence has shown that supporting cells proliferate and that new hair bundles can appear in vivo in the balance organs of mammals after antibiotic poisoning of hair cells. These findings suggest that hair cell regeneration may be induced in the ears of humans. In order to develop clinical therapies that will bring about hair cell regeneration in the human ear, we must identify the cellular and molecular signals responsible for triggering the regenerative proliferation of inner ear supporting cells after hair cell death, and determine how these cells go on to form hair cells. The goal of the proposed research is to identify factors that regulate regenerative replacement of hair cells in the ears of warm-blooded vertebrates during postembryonic life. This application proposes to investigate the following hypotheses: 1) Endogenous growth factors may negatively regulate inner-ear stem/progenitor cell proliferation, and 2) Robust regenerative proliferation of stem/progenitor cells in mature inner-ear SE may require a simultaneous release from negative regulation coupled with mitogenic signaling by the EGF and/or IGF pathways. These hypotheses will be tested using a combination of techniques, including expression profiling, cell localization, viral gene transfer, cell culture, and quantitative RT-PCR techniques. ? ? ?
| Luo, Chuan; Omelchenko, Irina; Manson, Robert et al. (2015) Direct Intracochlear Acoustic Stimulation Using a PZT Microactuator. Trends Hear 19: |
| Oesterle, Elizabeth C (2013) Changes in the adult vertebrate auditory sensory epithelium after trauma. Hear Res 297:91-8 |
| Oesterle, Elizabeth C; Chien, Wei-Ming; Campbell, Sean et al. (2011) p27(Kip1) is required to maintain proliferative quiescence in the adult cochlea and pituitary. Cell Cycle 10:1237-48 |
| Lin, Vincent; Golub, Justin S; Nguyen, Tot Bui et al. (2011) Inhibition of Notch activity promotes nonmitotic regeneration of hair cells in the adult mouse utricles. J Neurosci 31:15329-39 |
| McCullar, Jennifer S; Ty, Sidya; Campbell, Sean et al. (2010) Activin potentiates proliferation in mature avian auditory sensory epithelium. J Neurosci 30:478-90 |
| Lentz, Jennifer J; Gordon, William C; Farris, Hamilton E et al. (2010) Deafness and retinal degeneration in a novel USH1C knock-in mouse model. Dev Neurobiol 70:253-67 |
| McCullar, Jennifer S; Oesterle, Elizabeth C (2009) Cellular targets of estrogen signaling in regeneration of inner ear sensory epithelia. Hear Res 252:61-70 |
| Oesterle, Elizabeth C; Campbell, Sean (2009) Supporting cell characteristics in long-deafened aged mouse ears. J Assoc Res Otolaryngol 10:525-44 |
| Oesterle, Elizabeth C; Campbell, Sean; Taylor, Ruth R et al. (2008) Sox2 and JAGGED1 expression in normal and drug-damaged adult mouse inner ear. J Assoc Res Otolaryngol 9:65-89 |
| Bermingham-McDonogh, Olivia; Oesterle, Elizabeth C; Stone, Jennifer S et al. (2006) Expression of Prox1 during mouse cochlear development. J Comp Neurol 496:172-86 |
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